Figure 628

The kidney in sickle cell disease. Note the tubular deposition of hemosiderin. The principal renal lesion of hemoglobinopathy S is that of chronic TIN. By far more prevalent and severe in patients with sickle cell disease, variable degrees of TIN also are common in those with the sickle cell trait, sickle cell-hemoglobin C disease, or sickle cell-thalassemia disease. The predisposing factors that lead to a propensity of renal involvement are the physicochemical properties of hemoglobin S that predispose its polymerization in an environment of low oxygen tension, hypertonicity, and low pH. These conditions are characteristic of the renal medulla and therefore are conducive to the intraerythrocyte polymerization of hemoglobin S. The consequent erythrocyte sickling accounts for development of the typical vascular occlusive lesions. Although some of these changes occur in the cortex, the lesions begin and are predominantly located in the inner medulla, where they are at the core of the focal scarring and interstitial fibrosis. These lesions account for the common occurrence of papillary necrosis.

Examples of tubular functional abnormalities common and detectable early in the course of the disease are the following: impaired concentrating ability, depressed distal potassium and hydrogen secretion, tubular proteinuria, and decreased proximal reabsorption of phosphate, and increased secretion of uric acid and creatinine.